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Hippo signaling activates hedgehog signaling by Taz-driven Gli3 processing

The overlapping roles of Hippo and Hedgehog signaling in biological functions and diseases prompt us to investigate their potential interactions. Activation of Hippo signaling enhances the transcriptional output of Hedgehog signaling, and the role of Hippo signaling in regulating Hedgehog signaling...

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Autores principales: Tang, Chao, Wang, Jirong, Yao, Minli, Ji, Xing, Shi, Wei, Xu, Chengyun, Zeng, Ling-Hui, Wu, Ximei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Nature Singapore 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9889595/
https://www.ncbi.nlm.nih.gov/pubmed/36720733
http://dx.doi.org/10.1186/s13619-022-00151-6
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author Tang, Chao
Wang, Jirong
Yao, Minli
Ji, Xing
Shi, Wei
Xu, Chengyun
Zeng, Ling-Hui
Wu, Ximei
author_facet Tang, Chao
Wang, Jirong
Yao, Minli
Ji, Xing
Shi, Wei
Xu, Chengyun
Zeng, Ling-Hui
Wu, Ximei
author_sort Tang, Chao
collection PubMed
description The overlapping roles of Hippo and Hedgehog signaling in biological functions and diseases prompt us to investigate their potential interactions. Activation of Hippo signaling enhances the transcriptional output of Hedgehog signaling, and the role of Hippo signaling in regulating Hedgehog signaling relies on the Hippo pathway key effector, Taz. Interestingly, Taz exhibits a gradient expression across the posterior-to-anterior of limb bud mesoderms, similar to Sonic hedgehog (Shh). Importantly, Taz drives PKA to phosphorylate Gli3, resulting in the Gli3 processing into its repressor and attenuation of Hedgehog signaling in the Shh-independent manner. Specifically, Taz deletion in mouse embryonic limb bud mesenchyme not only enhances the Hedgehog signaling but partially restores the phenotypes from Shh deletion in causing severe defects of anteroposterior patterning and digit number and identity. Together, these results uncover Taz-dependent Gli3 processing as a hitherto uncharacterized mechanism controlling Hedgehog signaling, highlighting its cross-regulation by Hippo signaling. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13619-022-00151-6.
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spelling pubmed-98895952023-02-10 Hippo signaling activates hedgehog signaling by Taz-driven Gli3 processing Tang, Chao Wang, Jirong Yao, Minli Ji, Xing Shi, Wei Xu, Chengyun Zeng, Ling-Hui Wu, Ximei Cell Regen Research Article The overlapping roles of Hippo and Hedgehog signaling in biological functions and diseases prompt us to investigate their potential interactions. Activation of Hippo signaling enhances the transcriptional output of Hedgehog signaling, and the role of Hippo signaling in regulating Hedgehog signaling relies on the Hippo pathway key effector, Taz. Interestingly, Taz exhibits a gradient expression across the posterior-to-anterior of limb bud mesoderms, similar to Sonic hedgehog (Shh). Importantly, Taz drives PKA to phosphorylate Gli3, resulting in the Gli3 processing into its repressor and attenuation of Hedgehog signaling in the Shh-independent manner. Specifically, Taz deletion in mouse embryonic limb bud mesenchyme not only enhances the Hedgehog signaling but partially restores the phenotypes from Shh deletion in causing severe defects of anteroposterior patterning and digit number and identity. Together, these results uncover Taz-dependent Gli3 processing as a hitherto uncharacterized mechanism controlling Hedgehog signaling, highlighting its cross-regulation by Hippo signaling. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13619-022-00151-6. Springer Nature Singapore 2023-02-01 /pmc/articles/PMC9889595/ /pubmed/36720733 http://dx.doi.org/10.1186/s13619-022-00151-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Tang, Chao
Wang, Jirong
Yao, Minli
Ji, Xing
Shi, Wei
Xu, Chengyun
Zeng, Ling-Hui
Wu, Ximei
Hippo signaling activates hedgehog signaling by Taz-driven Gli3 processing
title Hippo signaling activates hedgehog signaling by Taz-driven Gli3 processing
title_full Hippo signaling activates hedgehog signaling by Taz-driven Gli3 processing
title_fullStr Hippo signaling activates hedgehog signaling by Taz-driven Gli3 processing
title_full_unstemmed Hippo signaling activates hedgehog signaling by Taz-driven Gli3 processing
title_short Hippo signaling activates hedgehog signaling by Taz-driven Gli3 processing
title_sort hippo signaling activates hedgehog signaling by taz-driven gli3 processing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9889595/
https://www.ncbi.nlm.nih.gov/pubmed/36720733
http://dx.doi.org/10.1186/s13619-022-00151-6
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